阿尔茨海默病中内质网应激-自噬溶酶体轴的作用及中医药调控机制OA
Role of endoplasmic reticulum stress-autophagy-lysosome axis in Alzheimer's disease and the regulatory mechanism of traditional Chinese medicine
蛋白质稳态失衡在阿尔茨海默病的发病机制中具有重要作用.内质网应激与自噬溶酶体通路功能障碍作为关键调控节点,通过双向反馈机制形成紧密的功能性交互网络,即内质网应激-自噬溶酶体轴.中医药干预可通过调节该轴的相互作用,减轻神经元损伤与死亡,从而改善认内质网应激-自噬溶酶体轴知功能损害.多种中药单体(如二氢青蒿素、齐墩果醇酸、姜黄素、藁本内酯、黄芩素等)能够通过调控GRP78、CHOP、LC3、LAMP1、p62等关键因子,协调内质网应激与自噬溶酶体通路之间的平衡;而中药复方(如黄连解毒汤、开心散、地黄饮子、加减薯蓣丸、黑逍遥散)经由PINK1-Parkin、ATF4-CHOP、IRE1-XBP1及mTOR等通路,缓解内质网应激并纠正自噬溶酶体功能缺陷,进而发挥神经保护效应.本文系统阐述内质网应激-自噬溶酶体轴在阿尔茨海默病发病过程中的相互作用及其中药调控机制,以期为阿尔茨海默病的防治策略及中医药现代化研究提供新的思路.
Protein homeostasis imbalance has recently been shown to play a significant role in the pathogenesis of Alzheimer's disease.Endoplasmic reticulum stress and autophagy-lysosomal pathway dysfunction serve as key regulatory nodes,forming a tightly functional interactive network via a bidirectional feedback mechanism referred to as the endoplasmic reticulum stress-autophagic lysosomal axis.Interventions using traditional Chinese medicine can regulate the interaction of this axis,alleviate neuronal damage and death,and thereby improve cognitive function impairment.Various single components of traditional Chinese medicine(e.g.,dihydroartemisinin,oleanolic acid,curcumin,ligustilide,and baicalin)can coordinate the balance between endoplasmic reticulum stress and autophagy-lysosomal pathways by regulating key factors such as GRP78,CHOP,LC3,LAMP1,and p62.In addition,traditional Chinese medicine combinations(e.g.,Huanglian Jiedu Decoction,Kai-xin-san,Dihuang Yinzi,Jiajian Shuyu Pill,and Heixiaoyao Power)exert neuroprotective effects by alleviating endoplasmic reticulum stress and correcting autophagolysosomal functional defects through pathways such as PINK1-Parkin,ATF4-CHOP,IRE1-XBP1,and mTOR.This review systematically considers the interaction between endoplasmic reticulum stress and the autophagic lysosomal axis in the pathogenesis of Alzheimer's disease,and the regulatory mechanisms of traditional Chinese medicine,with the aim of providing new ideas for the prevention and treatment of Alzheimer's disease and the modernization of research into traditional Chinese medicine.
常茜茜;刘冰心;吕怡琳;刘源;褚长松;马慧芬;宋军营
河南中医药大学中医药科学院,郑州 450046||豫药全产业链研发河南省协同创新中心,郑州 450046||中西医防治重大疾病河南省协同创新中心,郑州 450046河南中医药大学中医药科学院,郑州 450046||中西医防治重大疾病河南省协同创新中心,郑州 450046河南中医药大学中医药科学院,郑州 450046||豫药全产业链研发河南省协同创新中心,郑州 450046||中西医防治重大疾病河南省协同创新中心,郑州 450046河南中医药大学中医药科学院,郑州 450046||豫药全产业链研发河南省协同创新中心,郑州 450046||中西医防治重大疾病河南省协同创新中心,郑州 450046河南中医药大学中医药科学院,郑州 450046||豫药全产业链研发河南省协同创新中心,郑州 450046||中西医防治重大疾病河南省协同创新中心,郑州 450046河南中医药大学中医药科学院,郑州 450046||豫药全产业链研发河南省协同创新中心,郑州 450046||中西医防治重大疾病河南省协同创新中心,郑州 450046河南中医药大学中医药科学院,郑州 450046||豫药全产业链研发河南省协同创新中心,郑州 450046||中西医防治重大疾病河南省协同创新中心,郑州 450046
医药卫生
阿尔茨海默病内质网应激自噬溶酶体中医药
Alzheimer's diseaseendoplasmic reticulum stressautophagolysosometraditional Chinese medicine
《中国比较医学杂志》 2026 (9)
106-120,15
河南省自然科学基金(252300423162)河南省高校科技创新人才项目(25HASTIT062).
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